To understand the relationship between hypertension and insulin resistance we are identifying,cloning, and characterizing insulin regulated genes in vascular endothelium that may participate in insulin-stimulated nitric oxide production. We are using the differential display PCR method to identify genes from human umbilical vein endothelial cells and human aortic endothelial cells that are differentially regulated by insulin. Since small vessels dilate in response to insulin while large vessels constrict in response to insulin, we are particularly interested in genes that are induced by insulin in umbilical vein endothelium and repressed by insulin in aortic endothelium (or vice versa). The differential display PCR method is well suited for screening differences in mRNA due to differences in cell type or treatment. Candidate mRNAs can be conveniently cloned and sequenced. Full length cDNA for novel genes will be obtained by screening the appropriate cDNA library. We will then investigate the potential role of these genes in insulin-stimulated production of nitric oxide.